1. Field of the Invention
The present invention relates the c-ski gene. In particular, the present invention relates to DNA segments encoding chicken c-ski protein, to DNA constructs comprising the DNA segments and to cells transformed therewith. The present invention further relates to animals having increased muscle size and/or reduced amounts of fat.
2. Background Information
Viruses that contain the v-ski oncogene are not only capable of causing morphological transformation in vitro, but also can induce myogenic differentiation (Stavnezer et al., 1981, J. Virol. 39, 920-934; Li et al., 1986, J. Virol. 57, 1065-1072; Stavnezer et al., 1986, J. Virol. 57, 1073-1083; Colmenares and Stavnezer, 1989, Cell 59, 293-303). Viruses that carry and express c-ski cDNAs also induce foci and myogenic differentiation (Sutrave et al., 1990, Mol. Cell. Biol. 10, 3137-3144). This suggests the possibility that the ski oncogene is bifunctional since the two known functions of ski, transformation and differentiation, would appear to be contradictory properties. Using a v-ski probe, genomic clones for c-ski have been isolated and partially sequenced (Stavnezer et al., 1989, Mol. Cell. Biol. 9, 4038-4045). Comparisons of the properties of two forms of c-ski that are related by alternative splicing, and of several v-ski and c-ski deletion mutants have shown that the portions of ski required for transformation and differentiation are quite similar. These results suggest that the ability of c-ski and v-ski to cause transformation and induce differentiation may be related aspects of a single property of ski rather than two separate functions.
Relatively little is known about the biochemical functions of the ski proteins. All of the biologically active forms of c-ski and v-ski that have been studied are localized primarily in the nucleus (Barkas et al., 1986, Virology 151, 131-138; Sutrave et al., 1990, Mol. Cell. Biol. 10, 3137-3144). When the c-ski proteins are overexpressed in chicken cells, different forms of c-ski differ in their subnuclear localization; however, the significance of these differences, if any, is as yet unclear. when chromatin condenses for cell division, the over-expressed c-ski proteins are associated with the condensed chromatin (Sutrave et al., 1990, Mol. Cell. Biol. 10, 3137-3144). Biochemical studies have also shown that at least one form of c-ski can bind to DNA in the presence of other proteins (Nagase et al., 1990, Nucl. Acids Res. 18, 337-343).
None of the available data make it possible to infer the normal function of c-ski either in terms of its role in growth and development (if any) or to have any direct insight into its mode of action.